a study to evaluate the safety and efficacy of itacitinib in moderate to severe ulcerative colitis

Conditions: Moderate to Severe Ulcerative Colitis

Summary: the purpose of this study is to evaluate the efficacy and safety of itacitinib in participants with moderate to severe ulcerative colitis (uc).


Eligibility criteria:
inclusion criteria: * confirmed diagnosis of uc at least 12 weeks before screening based on clinical, endoscopic, and histopathological evidence. * have a 3-component mayo score of 4 to 9, which includes a modified mayo endoscopy score (mmes) of ≥ 2 as determined by a central reader, a rectal bleeding score of ≥ 1, and a stool frequency score of ≥ 1. * must have failed or be intolerant to (discontinued the medication due to an adverse event as determined by the investigator) at least 1 of the following treatments for uc: oral corticosteroids, azathioprine or 6-mercaptopurine, biologic therapy (eg, infliximab, vedolizumab or adalimumab). * participants currently receiving the following treatment(s) for uc are eligible, provided they have been receiving acceptable and stable dose(s): oral 5-asa or oral corticosteroids. * no evidence of active or latent or inadequately treated tuberculosis infection. * willingness to avoid pregnancy or fathering children. exclusion criteria: * clinical signs of fulminant colitis or toxic megacolon. * presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, or clinical or radiographic findings suggestive of crohn's disease. * disease limited to the distal 15 cm of the colon. * receiving (or expected to receive) the following therapies within protocol-designated timeframes before the baseline visit or during the study: natalizumab; anti-tnf therapy; vedolizumab or any investigational anti-adhesion molecule therapy; ustekinumab or any on or off label biologic therapy; interferon therapy; cyclosporine, mycophenolate, or tacrolimus; daily dose of oral corticosteroids ≥ 25 mg prednisone or equivalent; intravenous corticosteroids; rectally administered formulation of corticosteroids or 5-aminosalicylic acid; and aza, 6-mp, or methotrexate. * enema treatments within 2 weeks of the baseline visit, with the exception of enema bowel preparations for clinical assessments. * positive stool examinations for enteric pathogens, pathogenic ova or parasites, or clostridium difficile toxin at the screening visit. * other immunocompromised states and history of opportunistic infections. * history of stomach or intestinal surgery, including bariatric surgery (note: appendectomy and/or cholecystectomy, is allowed). o surgery for uc or likely to require surgery for uc during the study. * if at risk for colorectal cancer, must have had a colonoscopy within protocol-defined timeframes. * history of recurrent, disseminated, or multiple dermatomal herpes zoster. * history of alcohol or drug abuse. * history of active malignancy within 5 years of screening, excluding superficial basal and squamous cell carcinoma of the skin and adequately treated carcinoma in situ of the cervix. * current or recent history (within 30 days before randomization) of a clinically meaningful viral, bacterial, fungal, parasitic, or mycobacterial infection. * previously received either lymphocyte apheresis or selective monocyte granulocyte apheresis (eg, cellsorba) within 1 year of baseline. * history of unstable ischemic heart disease or uncontrolled hypertension. * positive serology test results for hiv, for hepatitis b surface antigen or core antibody, or for hcv antibody with detectable rna at screening. * participants taking potent systemic cyp3a4 inhibitors or inducers or fluconazole within 2 weeks or 5 half-lives (whichever is longer) of baseline. * participants taking p-gp substrates with narrow therapeutic index, including digoxin within 2 weeks or 5 half-lives (whichever is longer) of baseline.

Keywords: inflammatory bowel disease ulcerative colitis janus kinase inhibitor jak1